JP5006799B2 - 神経疾患及び精神神経疾患の処置用のグリシントランスポーター1(glyt−1)阻害剤としての[4−(ヘテロアリール)ピペラジン−1−イル]−(2,5−置換フェニル)−メタノン誘導体 - Google Patents
神経疾患及び精神神経疾患の処置用のグリシントランスポーター1(glyt−1)阻害剤としての[4−(ヘテロアリール)ピペラジン−1−イル]−(2,5−置換フェニル)−メタノン誘導体 Download PDFInfo
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- JP5006799B2 JP5006799B2 JP2007549824A JP2007549824A JP5006799B2 JP 5006799 B2 JP5006799 B2 JP 5006799B2 JP 2007549824 A JP2007549824 A JP 2007549824A JP 2007549824 A JP2007549824 A JP 2007549824A JP 5006799 B2 JP5006799 B2 JP 5006799B2
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- Prior art keywords
- methanesulfonyl
- phenyl
- thiazol
- piperazin
- methanone
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Expired - Fee Related
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- 125000001997 phenyl group Chemical class [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 title claims description 6
- 108010063380 Glycine Plasma Membrane Transport Proteins Proteins 0.000 title description 22
- 102000010726 Glycine Plasma Membrane Transport Proteins Human genes 0.000 title description 20
- 239000003112 inhibitor Substances 0.000 title description 8
- 230000000926 neurological effect Effects 0.000 title description 3
- 125000001072 heteroaryl group Chemical group 0.000 title 1
- 125000004194 piperazin-1-yl group Chemical group [H]N1C([H])([H])C([H])([H])N(*)C([H])([H])C1([H])[H] 0.000 title 1
- 150000001875 compounds Chemical class 0.000 claims description 276
- -1 4-methyl-5-trifluoromethyl-thiazol-2-yl Chemical group 0.000 claims description 87
- 125000000217 alkyl group Chemical group 0.000 claims description 55
- 150000002367 halogens Chemical group 0.000 claims description 31
- 229910052736 halogen Inorganic materials 0.000 claims description 29
- 150000003839 salts Chemical class 0.000 claims description 26
- DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 claims description 20
- 238000000034 method Methods 0.000 claims description 17
- 239000002253 acid Substances 0.000 claims description 15
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 14
- 201000000980 schizophrenia Diseases 0.000 claims description 14
- 239000004471 Glycine Substances 0.000 claims description 11
- 239000003814 drug Substances 0.000 claims description 11
- 201000010099 disease Diseases 0.000 claims description 10
- 208000028017 Psychotic disease Diseases 0.000 claims description 9
- 125000001424 substituent group Chemical group 0.000 claims description 9
- 208000024827 Alzheimer disease Diseases 0.000 claims description 8
- 230000019771 cognition Effects 0.000 claims description 7
- 125000000592 heterocycloalkyl group Chemical group 0.000 claims description 7
- 206010012289 Dementia Diseases 0.000 claims description 6
- 125000004435 hydrogen atom Chemical class [H]* 0.000 claims description 6
- 208000006096 Attention Deficit Disorder with Hyperactivity Diseases 0.000 claims description 5
- 239000001257 hydrogen Substances 0.000 claims description 5
- 229910052739 hydrogen Inorganic materials 0.000 claims description 5
- 230000001771 impaired effect Effects 0.000 claims description 5
- 238000002360 preparation method Methods 0.000 claims description 5
- IKFUFYQXBJCAPV-UHFFFAOYSA-N (5-methylsulfonyl-2-propan-2-yloxyphenyl)-[4-[5-(trifluoromethyl)-1,3,4-thiadiazol-2-yl]piperazin-1-yl]methanone Chemical compound CC(C)OC1=CC=C(S(C)(=O)=O)C=C1C(=O)N1CCN(C=2SC(=NN=2)C(F)(F)F)CC1 IKFUFYQXBJCAPV-UHFFFAOYSA-N 0.000 claims description 4
- BVSQFBYKCVMYBI-UHFFFAOYSA-N 2-[4-[2-(cyclobutylmethoxy)-5-methylsulfonylbenzoyl]piperazin-1-yl]-1,3-thiazole-5-carbonitrile Chemical compound C1CN(C=2SC(=CN=2)C#N)CCN1C(=O)C1=CC(S(=O)(=O)C)=CC=C1OCC1CCC1 BVSQFBYKCVMYBI-UHFFFAOYSA-N 0.000 claims description 4
- 208000036864 Attention deficit/hyperactivity disease Diseases 0.000 claims description 4
- QLTKPVOXXXMHFU-UHFFFAOYSA-N [4-[5-(benzenesulfonyl)-1,3-thiazol-2-yl]piperazin-1-yl]-(5-methylsulfonyl-2-propan-2-yloxyphenyl)methanone Chemical compound CC(C)OC1=CC=C(S(C)(=O)=O)C=C1C(=O)N1CCN(C=2SC(=CN=2)S(=O)(=O)C=2C=CC=CC=2)CC1 QLTKPVOXXXMHFU-UHFFFAOYSA-N 0.000 claims description 4
- CUMLRBPVDDJGBG-UHFFFAOYSA-N [5-methylsulfonyl-2-(1,1,1-trifluoropropan-2-yloxy)phenyl]-[4-[5-(2,2,2-trifluoroethyl)-1,3-thiazol-2-yl]piperazin-1-yl]methanone Chemical compound FC(F)(F)C(C)OC1=CC=C(S(C)(=O)=O)C=C1C(=O)N1CCN(C=2SC(CC(F)(F)F)=CN=2)CC1 CUMLRBPVDDJGBG-UHFFFAOYSA-N 0.000 claims description 4
- 208000015802 attention deficit-hyperactivity disease Diseases 0.000 claims description 4
- 208000035231 inattentive type attention deficit hyperactivity disease Diseases 0.000 claims description 4
- 230000005764 inhibitory process Effects 0.000 claims description 4
- ZVTDDYJHXJEJKO-UHFFFAOYSA-N (5-methylsulfonyl-2-propan-2-yloxyphenyl)-[4-(3-phenyl-1,2,4-thiadiazol-5-yl)piperazin-1-yl]methanone Chemical compound CC(C)OC1=CC=C(S(C)(=O)=O)C=C1C(=O)N1CCN(C=2SN=C(N=2)C=2C=CC=CC=2)CC1 ZVTDDYJHXJEJKO-UHFFFAOYSA-N 0.000 claims description 3
- IWUJIAYWHNSPPF-UHFFFAOYSA-N (5-methylsulfonyl-2-propan-2-ylsulfanylphenyl)-[4-[5-(trifluoromethyl)-1,3-thiazol-2-yl]piperazin-1-yl]methanone Chemical compound CC(C)SC1=CC=C(S(C)(=O)=O)C=C1C(=O)N1CCN(C=2SC(=CN=2)C(F)(F)F)CC1 IWUJIAYWHNSPPF-UHFFFAOYSA-N 0.000 claims description 3
- HERSANSGUAIDBH-UHFFFAOYSA-N 2-[4-[2-(2,2-dimethylpropoxy)-5-methylsulfonylbenzoyl]piperazin-1-yl]-1,3-thiazole-5-carbonitrile Chemical compound CC(C)(C)COC1=CC=C(S(C)(=O)=O)C=C1C(=O)N1CCN(C=2SC(=CN=2)C#N)CC1 HERSANSGUAIDBH-UHFFFAOYSA-N 0.000 claims description 3
- XCDMPWPHHBEQOS-UHFFFAOYSA-N 2-[4-[2-(2-methylpropoxy)-5-methylsulfonylbenzoyl]piperazin-1-yl]-1,3-thiazole-5-carbonitrile Chemical compound CC(C)COC1=CC=C(S(C)(=O)=O)C=C1C(=O)N1CCN(C=2SC(=CN=2)C#N)CC1 XCDMPWPHHBEQOS-UHFFFAOYSA-N 0.000 claims description 3
- ZRNNGAYKLRUQHB-UHFFFAOYSA-N 2-[4-[5-methylsulfonyl-2-(1,1,1-trifluoropropan-2-yloxy)benzoyl]piperazin-1-yl]-1,3-thiazole-5-carbonitrile Chemical compound FC(F)(F)C(C)OC1=CC=C(S(C)(=O)=O)C=C1C(=O)N1CCN(C=2SC(=CN=2)C#N)CC1 ZRNNGAYKLRUQHB-UHFFFAOYSA-N 0.000 claims description 3
- ASIFVCSFQDKGIJ-UHFFFAOYSA-N 4-cyclopentyloxy-n-methyl-3-[4-(3-phenyl-1,2,4-thiadiazol-5-yl)piperazine-1-carbonyl]benzenesulfonamide Chemical compound C1CN(C=2SN=C(N=2)C=2C=CC=CC=2)CCN1C(=O)C1=CC(S(=O)(=O)NC)=CC=C1OC1CCCC1 ASIFVCSFQDKGIJ-UHFFFAOYSA-N 0.000 claims description 3
- 208000002193 Pain Diseases 0.000 claims description 3
- WIXPCXUVIOSNDP-UHFFFAOYSA-N [2-(2-methylpropoxy)-5-methylsulfonylphenyl]-[4-[5-(trifluoromethyl)-1,3,4-thiadiazol-2-yl]piperazin-1-yl]methanone Chemical compound CC(C)COC1=CC=C(S(C)(=O)=O)C=C1C(=O)N1CCN(C=2SC(=NN=2)C(F)(F)F)CC1 WIXPCXUVIOSNDP-UHFFFAOYSA-N 0.000 claims description 3
- CRRCRADOFQQFKN-UHFFFAOYSA-N [2-(cyclopropylmethoxy)-5-methylsulfonylphenyl]-[4-[5-(trifluoromethyl)-1,3,4-thiadiazol-2-yl]piperazin-1-yl]methanone Chemical compound C1CN(C=2SC(=NN=2)C(F)(F)F)CCN1C(=O)C1=CC(S(=O)(=O)C)=CC=C1OCC1CC1 CRRCRADOFQQFKN-UHFFFAOYSA-N 0.000 claims description 3
- HBAKLKBWBGRRFU-CYBMUJFWSA-N [2-[(2r)-butan-2-yl]oxy-5-methylsulfonylphenyl]-[4-[5-(trifluoromethyl)-1,3-thiazol-2-yl]piperazin-1-yl]methanone Chemical compound CC[C@@H](C)OC1=CC=C(S(C)(=O)=O)C=C1C(=O)N1CCN(C=2SC(=CN=2)C(F)(F)F)CC1 HBAKLKBWBGRRFU-CYBMUJFWSA-N 0.000 claims description 3
- HBAKLKBWBGRRFU-ZDUSSCGKSA-N [2-[(2s)-butan-2-yl]oxy-5-methylsulfonylphenyl]-[4-[5-(trifluoromethyl)-1,3-thiazol-2-yl]piperazin-1-yl]methanone Chemical compound CC[C@H](C)OC1=CC=C(S(C)(=O)=O)C=C1C(=O)N1CCN(C=2SC(=CN=2)C(F)(F)F)CC1 HBAKLKBWBGRRFU-ZDUSSCGKSA-N 0.000 claims description 3
- MCWCOEUMJMMRQF-UHFFFAOYSA-N [4-(5-butylsulfonyl-1,3-thiazol-2-yl)piperazin-1-yl]-(2-cyclopentyloxy-5-methylsulfonylphenyl)methanone Chemical compound S1C(S(=O)(=O)CCCC)=CN=C1N1CCN(C(=O)C=2C(=CC=C(C=2)S(C)(=O)=O)OC2CCCC2)CC1 MCWCOEUMJMMRQF-UHFFFAOYSA-N 0.000 claims description 3
- ABWADBNJTCCZMY-UHFFFAOYSA-N [4-(5-butylsulfonyl-1,3-thiazol-2-yl)piperazin-1-yl]-[2-(2,2-dimethylpropoxy)-5-methylsulfonylphenyl]methanone Chemical compound S1C(S(=O)(=O)CCCC)=CN=C1N1CCN(C(=O)C=2C(=CC=C(C=2)S(C)(=O)=O)OCC(C)(C)C)CC1 ABWADBNJTCCZMY-UHFFFAOYSA-N 0.000 claims description 3
- IBDFDOWSFDLYRD-UHFFFAOYSA-N [4-[5-(benzenesulfonyl)-1,3-thiazol-2-yl]piperazin-1-yl]-(2-cyclopentyloxy-5-methylsulfonylphenyl)methanone Chemical compound C1CN(C=2SC(=CN=2)S(=O)(=O)C=2C=CC=CC=2)CCN1C(=O)C1=CC(S(=O)(=O)C)=CC=C1OC1CCCC1 IBDFDOWSFDLYRD-UHFFFAOYSA-N 0.000 claims description 3
- JQMPBTUJLBSOGH-UHFFFAOYSA-N [4-[5-(benzenesulfonyl)-1,3-thiazol-2-yl]piperazin-1-yl]-[2-(2,2-dimethylpropoxy)-5-methylsulfonylphenyl]methanone Chemical compound CC(C)(C)COC1=CC=C(S(C)(=O)=O)C=C1C(=O)N1CCN(C=2SC(=CN=2)S(=O)(=O)C=2C=CC=CC=2)CC1 JQMPBTUJLBSOGH-UHFFFAOYSA-N 0.000 claims description 3
- YDFGSIGVIRKIEN-UHFFFAOYSA-N [4-[5-(benzenesulfonyl)-1,3-thiazol-2-yl]piperazin-1-yl]-[2-(2-methylpropoxy)-5-methylsulfonylphenyl]methanone Chemical compound CC(C)COC1=CC=C(S(C)(=O)=O)C=C1C(=O)N1CCN(C=2SC(=CN=2)S(=O)(=O)C=2C=CC=CC=2)CC1 YDFGSIGVIRKIEN-UHFFFAOYSA-N 0.000 claims description 3
- TWGZDUQQJGZIJT-UHFFFAOYSA-N [5-ethylsulfonyl-2-(1,1,1-trifluoropropan-2-yloxy)phenyl]-[4-[5-(trifluoromethyl)-1,3-thiazol-2-yl]piperazin-1-yl]methanone Chemical compound CCS(=O)(=O)C1=CC=C(OC(C)C(F)(F)F)C(C(=O)N2CCN(CC2)C=2SC(=CN=2)C(F)(F)F)=C1 TWGZDUQQJGZIJT-UHFFFAOYSA-N 0.000 claims description 3
- LEBKWLWANQPIGD-UHFFFAOYSA-N [5-methylsulfonyl-2-(1,1,1-trifluoropropan-2-yloxy)phenyl]-[4-[5-(trifluoromethyl)-1,3-thiazol-2-yl]piperazin-1-yl]methanone Chemical compound FC(F)(F)C(C)OC1=CC=C(S(C)(=O)=O)C=C1C(=O)N1CCN(C=2SC(=CN=2)C(F)(F)F)CC1 LEBKWLWANQPIGD-UHFFFAOYSA-N 0.000 claims description 3
- MGYAQKMPOBJXAM-UHFFFAOYSA-N [5-methylsulfonyl-2-(1,1,1-trifluoropropan-2-yloxy)phenyl]-[4-[5-methyl-4-(trifluoromethyl)-1,3-thiazol-2-yl]piperazin-1-yl]methanone Chemical compound FC(F)(F)C(C)OC1=CC=C(S(C)(=O)=O)C=C1C(=O)N1CCN(C=2SC(C)=C(N=2)C(F)(F)F)CC1 MGYAQKMPOBJXAM-UHFFFAOYSA-N 0.000 claims description 3
- MIMSTDIRRYJJJA-GFCCVEGCSA-N [5-methylsulfonyl-2-[(2r)-1,1,1-trifluoropropan-2-yl]oxyphenyl]-[4-[4-methyl-5-(trifluoromethyl)-1,3-thiazol-2-yl]piperazin-1-yl]methanone Chemical compound FC(F)(F)[C@@H](C)OC1=CC=C(S(C)(=O)=O)C=C1C(=O)N1CCN(C=2SC(=C(C)N=2)C(F)(F)F)CC1 MIMSTDIRRYJJJA-GFCCVEGCSA-N 0.000 claims description 3
- CUMLRBPVDDJGBG-GFCCVEGCSA-N [5-methylsulfonyl-2-[(2r)-1,1,1-trifluoropropan-2-yl]oxyphenyl]-[4-[5-(2,2,2-trifluoroethyl)-1,3-thiazol-2-yl]piperazin-1-yl]methanone Chemical compound FC(F)(F)[C@@H](C)OC1=CC=C(S(C)(=O)=O)C=C1C(=O)N1CCN(C=2SC(CC(F)(F)F)=CN=2)CC1 CUMLRBPVDDJGBG-GFCCVEGCSA-N 0.000 claims description 3
- LEBKWLWANQPIGD-LLVKDONJSA-N [5-methylsulfonyl-2-[(2r)-1,1,1-trifluoropropan-2-yl]oxyphenyl]-[4-[5-(trifluoromethyl)-1,3-thiazol-2-yl]piperazin-1-yl]methanone Chemical compound FC(F)(F)[C@@H](C)OC1=CC=C(S(C)(=O)=O)C=C1C(=O)N1CCN(C=2SC(=CN=2)C(F)(F)F)CC1 LEBKWLWANQPIGD-LLVKDONJSA-N 0.000 claims description 3
- MIMSTDIRRYJJJA-LBPRGKRZSA-N [5-methylsulfonyl-2-[(2s)-1,1,1-trifluoropropan-2-yl]oxyphenyl]-[4-[4-methyl-5-(trifluoromethyl)-1,3-thiazol-2-yl]piperazin-1-yl]methanone Chemical compound FC(F)(F)[C@H](C)OC1=CC=C(S(C)(=O)=O)C=C1C(=O)N1CCN(C=2SC(=C(C)N=2)C(F)(F)F)CC1 MIMSTDIRRYJJJA-LBPRGKRZSA-N 0.000 claims description 3
- CUMLRBPVDDJGBG-LBPRGKRZSA-N [5-methylsulfonyl-2-[(2s)-1,1,1-trifluoropropan-2-yl]oxyphenyl]-[4-[5-(2,2,2-trifluoroethyl)-1,3-thiazol-2-yl]piperazin-1-yl]methanone Chemical compound FC(F)(F)[C@H](C)OC1=CC=C(S(C)(=O)=O)C=C1C(=O)N1CCN(C=2SC(CC(F)(F)F)=CN=2)CC1 CUMLRBPVDDJGBG-LBPRGKRZSA-N 0.000 claims description 3
- LEBKWLWANQPIGD-NSHDSACASA-N [5-methylsulfonyl-2-[(2s)-1,1,1-trifluoropropan-2-yl]oxyphenyl]-[4-[5-(trifluoromethyl)-1,3-thiazol-2-yl]piperazin-1-yl]methanone Chemical compound FC(F)(F)[C@H](C)OC1=CC=C(S(C)(=O)=O)C=C1C(=O)N1CCN(C=2SC(=CN=2)C(F)(F)F)CC1 LEBKWLWANQPIGD-NSHDSACASA-N 0.000 claims description 3
- 230000004064 dysfunction Effects 0.000 claims description 3
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- 239000013058 crude material Substances 0.000 description 138
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- UTERCAIZUWWRFV-UHFFFAOYSA-N tert-butyl 4-[5-(2,2,2-trifluoroethyl)-1,3-thiazol-2-yl]piperazine-1-carboxylate Chemical compound C1CN(C(=O)OC(C)(C)C)CCN1C1=NC=C(CC(F)(F)F)S1 UTERCAIZUWWRFV-UHFFFAOYSA-N 0.000 description 1
- HLXYMQUOAUDZQC-UHFFFAOYSA-N tert-butyl 4-[5-(2,2-difluoroethenyl)-1,3-thiazol-2-yl]piperazine-1-carboxylate Chemical compound C1CN(C(=O)OC(C)(C)C)CCN1C1=NC=C(C=C(F)F)S1 HLXYMQUOAUDZQC-UHFFFAOYSA-N 0.000 description 1
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- ZARFVKVJDVWDGR-UHFFFAOYSA-N tert-butyl 4-[5-(benzenesulfonyl)-1,3-thiazol-2-yl]piperazine-1-carboxylate Chemical compound C1CN(C(=O)OC(C)(C)C)CCN1C1=NC=C(S(=O)(=O)C=2C=CC=CC=2)S1 ZARFVKVJDVWDGR-UHFFFAOYSA-N 0.000 description 1
- MDXLLRBMODVVHW-UHFFFAOYSA-N tert-butyl 4-[5-(hydroxymethyl)-1,3-thiazol-2-yl]piperazine-1-carboxylate Chemical compound C1CN(C(=O)OC(C)(C)C)CCN1C1=NC=C(CO)S1 MDXLLRBMODVVHW-UHFFFAOYSA-N 0.000 description 1
- JWXJQJRRQURNLI-UHFFFAOYSA-N tert-butyl 4-[5-(trifluoromethyl)-1,3,4-thiadiazol-2-yl]piperazine-1-carboxylate Chemical compound C1CN(C(=O)OC(C)(C)C)CCN1C1=NN=C(C(F)(F)F)S1 JWXJQJRRQURNLI-UHFFFAOYSA-N 0.000 description 1
- 125000005931 tert-butyloxycarbonyl group Chemical group [H]C([H])([H])C(OC(*)=O)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 125000003718 tetrahydrofuranyl group Chemical group 0.000 description 1
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- 210000001519 tissue Anatomy 0.000 description 1
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Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D285/00—Heterocyclic compounds containing rings having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by groups C07D275/00 - C07D283/00
- C07D285/01—Five-membered rings
- C07D285/02—Thiadiazoles; Hydrogenated thiadiazoles
- C07D285/04—Thiadiazoles; Hydrogenated thiadiazoles not condensed with other rings
- C07D285/08—1,2,4-Thiadiazoles; Hydrogenated 1,2,4-thiadiazoles
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
- A61K31/433—Thidiazoles
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/04—Centrally acting analgesics, e.g. opioids
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/18—Antipsychotics, i.e. neuroleptics; Drugs for mania or schizophrenia
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/28—Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D277/00—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings
- C07D277/02—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings
- C07D277/20—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
- C07D277/32—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D277/38—Nitrogen atoms
- C07D277/42—Amino or imino radicals substituted by hydrocarbon or substituted hydrocarbon radicals
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D277/00—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings
- C07D277/02—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings
- C07D277/20—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
- C07D277/32—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D277/56—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D285/00—Heterocyclic compounds containing rings having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by groups C07D275/00 - C07D283/00
- C07D285/01—Five-membered rings
- C07D285/02—Thiadiazoles; Hydrogenated thiadiazoles
- C07D285/04—Thiadiazoles; Hydrogenated thiadiazoles not condensed with other rings
- C07D285/12—1,3,4-Thiadiazoles; Hydrogenated 1,3,4-thiadiazoles
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D285/00—Heterocyclic compounds containing rings having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by groups C07D275/00 - C07D283/00
- C07D285/01—Five-membered rings
- C07D285/02—Thiadiazoles; Hydrogenated thiadiazoles
- C07D285/04—Thiadiazoles; Hydrogenated thiadiazoles not condensed with other rings
- C07D285/12—1,3,4-Thiadiazoles; Hydrogenated 1,3,4-thiadiazoles
- C07D285/125—1,3,4-Thiadiazoles; Hydrogenated 1,3,4-thiadiazoles with oxygen, sulfur or nitrogen atoms, directly attached to ring carbon atoms, the nitrogen atoms not forming part of a nitro radical
- C07D285/135—Nitrogen atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
- C07D417/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings
- C07D417/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings linked by a chain containing hetero atoms as chain links
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Applications Claiming Priority (3)
Application Number | Priority Date | Filing Date | Title |
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EP05100077 | 2005-01-07 | ||
EP05100077.6 | 2005-01-07 | ||
PCT/EP2005/014082 WO2006072436A1 (en) | 2005-01-07 | 2005-12-28 | [4-(heteroaryl) piperazin-1-yl]-(2,5-substituted -phenyl)methanone derivatives as glycine transporter 1 (glyt-1) inhibitors for the treatment of neurological and neuropsychiatric disorders |
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JP2008526796A JP2008526796A (ja) | 2008-07-24 |
JP5006799B2 true JP5006799B2 (ja) | 2012-08-22 |
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JP2007549824A Expired - Fee Related JP5006799B2 (ja) | 2005-01-07 | 2005-12-28 | 神経疾患及び精神神経疾患の処置用のグリシントランスポーター1(glyt−1)阻害剤としての[4−(ヘテロアリール)ピペラジン−1−イル]−(2,5−置換フェニル)−メタノン誘導体 |
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US (1) | US7220744B2 (zh) |
EP (1) | EP1838308B1 (zh) |
JP (1) | JP5006799B2 (zh) |
KR (1) | KR100895752B1 (zh) |
CN (1) | CN101137363B (zh) |
AR (1) | AR052866A1 (zh) |
AT (1) | ATE472327T1 (zh) |
AU (1) | AU2005324024B2 (zh) |
BR (1) | BRPI0519794A2 (zh) |
CA (1) | CA2593463C (zh) |
DE (1) | DE602005022113D1 (zh) |
ES (1) | ES2346335T3 (zh) |
IL (1) | IL184353A (zh) |
MX (1) | MX2007008189A (zh) |
NO (1) | NO20073667L (zh) |
RU (1) | RU2396270C2 (zh) |
TW (1) | TWI313174B (zh) |
WO (1) | WO2006072436A1 (zh) |
ZA (1) | ZA200705472B (zh) |
Families Citing this family (29)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US20050119251A1 (en) * | 2001-12-21 | 2005-06-02 | Jian-Min Fu | Nicotinamide derivatives and their use as therapeutic agents |
CA2580856A1 (en) | 2004-09-20 | 2006-03-30 | Xenon Pharmaceuticals Inc. | Heterocyclic derivatives and their use as stearoyl-coa desaturase inhibitors |
TW200626139A (en) | 2004-09-20 | 2006-08-01 | Xenon Pharmaceuticals Inc | Heterocyclic derivatives and their use as therapeutic agents |
AR051294A1 (es) * | 2004-09-20 | 2007-01-03 | Xenon Pharmaceuticals Inc | Derivados heterociclicos y su uso como inhibidores de la estearoil-coa desaturasa |
US7951805B2 (en) * | 2004-09-20 | 2011-05-31 | Xenon Pharmaceuticals Inc. | Heterocyclic derivatives and their use as mediators of stearoyl-CoA desaturase |
BRPI0515483A (pt) * | 2004-09-20 | 2008-07-22 | Xenon Pharmaceuticals Inc | derivados heterocìclicos para o tratamento de doenças mediadas por enzimas estearoil-coa desaturase |
BRPI0611187A2 (pt) | 2005-06-03 | 2010-08-24 | Xenon Pharmaceuticals Inc | derivados aminotiazàis como inibidores da estearoil-coa desaturase humana |
EP2131843B1 (en) | 2007-03-05 | 2011-11-09 | F. Hoffmann-La Roche AG | Process for the synthesis of glyt-1 inhibitors |
WO2010040663A1 (en) | 2008-10-09 | 2010-04-15 | F. Hoffmann-La Roche Ag | Pyrrolidine n-benzyl derivatives |
TW201127806A (en) * | 2009-09-02 | 2011-08-16 | Du Pont | Process for the synthesis of fluorinated ethers of aromatic acids |
TW201127805A (en) * | 2009-09-02 | 2011-08-16 | Du Pont | Process for the synthesis of fluorinated ethers of aromatic acids |
WO2011082660A1 (zh) * | 2010-01-08 | 2011-07-14 | 中国科学院上海有机化学研究所 | 5-多氟烷基取代的2-氨基噻唑类化合物、合成方法及其应用 |
CN101885708B (zh) * | 2010-07-07 | 2013-03-06 | 中国科学院上海有机化学研究所 | 5-多氟烷基取代的2-氨基噻唑类化合物、合成方法及其应用 |
SG186885A1 (en) * | 2010-06-04 | 2013-02-28 | Albany Molecular Res Inc | Glycine transporter-1 inhibitors, methods of making them, and uses thereof |
US9012489B2 (en) * | 2011-08-03 | 2015-04-21 | Boehringer Ingelheim International Gmbh | Phenyl-3-aza-bicyclo[3.1.0]hex-3-yl-methanones and the use thereof as medicament |
US9266838B2 (en) | 2011-08-15 | 2016-02-23 | University Of Utah Research Foundation | Substituted (E)-N′-(1-phenylethylidene)benzohydrazide analogs as histone demethylase inhibitors |
AU2012296804B2 (en) * | 2011-08-17 | 2017-04-20 | Remynd Nv | Piperazine thiazole derivatives useful in the treatment of tauopathies such as alzheimer's disease |
CN104119343A (zh) * | 2013-04-25 | 2014-10-29 | 苏州科捷生物医药有限公司 | 2-三氟甲基噻二唑类化合物及其用途 |
EP3010915B1 (en) * | 2013-06-19 | 2019-05-08 | University of Utah Research Foundation | Substituted (3-(5-chloro-2-hydroxyphenyl)-1-benzoyl-1h-pyrazole compounds as histone demethylase inhibitors |
EP3134406A1 (en) | 2014-04-24 | 2017-03-01 | Dart Neuroscience (Cayman) Ltd | Substituted 2,4,5,6-tetrahydropyrrolo[3,4-c]pyrazole and 4,5,6,7-tetrahydro-2h-pyrazolo [4,3-c]pyridine compounds as glyt1 inhibitors |
EP3215500A1 (en) | 2014-11-05 | 2017-09-13 | Dart NeuroScience (Cayman) Ltd. | Substituted azetidinyl compounds as glyt1 inhibitors |
CN105712945B (zh) * | 2014-12-22 | 2020-12-01 | 上海翰森生物医药科技有限公司 | 2-取代氧基-5-甲砜基芳基哌嗪酰胺类似物及其制备方法和用途 |
CN105712952B (zh) * | 2014-12-22 | 2021-03-26 | 上海翰森生物医药科技有限公司 | 2-取代氧基-5-甲砜基苯基哌嗪酰胺类似物及其制备方法和用途 |
MA46589A (fr) * | 2016-10-24 | 2019-08-28 | Yumanity Therapeutics Inc | Composés et utilisations de ces derniers |
US11873298B2 (en) | 2017-10-24 | 2024-01-16 | Janssen Pharmaceutica Nv | Compounds and uses thereof |
EP3914593A4 (en) | 2019-01-24 | 2022-11-02 | Yumanity Therapeutics, Inc. | COMPOUNDS AND THEIR USES |
DK3966206T3 (da) | 2019-05-10 | 2023-11-13 | Deciphera Pharmaceuticals Llc | Heteroarylaminopyrimidinamid-autophagihæmmere og fremgangsmåder til anvendelse deraf |
JP2022536540A (ja) | 2019-06-17 | 2022-08-17 | デシフェラ・ファーマシューティカルズ,エルエルシー | アミノピリミジンアミドオートファジー阻害剤およびその使用方法 |
CA3188340A1 (en) | 2020-08-13 | 2022-02-17 | Boehringer Ingelheim International Gmbh | Treatment of cognitive impairement associated with schizophrenia |
Family Cites Families (16)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
GB867273A (en) * | 1959-02-20 | 1961-05-03 | Wallace & Tiernan Inc | Piperazine derivatives |
DE2423847A1 (de) | 1973-05-28 | 1975-01-02 | Ciba Geigy Ag | Neue sulfamoylbenzoesaeureamide |
DE2611705A1 (de) | 1976-03-18 | 1977-09-22 | Josef Dipl Chem Dr Rer N Klosa | N-5-(nitrofurfuryliden-)-1-amino- hydantoin enthaltende kristalloesungsmittel |
IT1176613B (it) | 1984-08-14 | 1987-08-18 | Ravizza Spa | Derivati piperazinici farmacologicamente attivi e processo per la loro preparazione |
RU2124511C1 (ru) | 1993-05-14 | 1999-01-10 | Фармасьютикал Ко., Лтд | Производные пиперазина |
JP2002505332A (ja) | 1998-03-06 | 2002-02-19 | ジヤンセン・フアーマシユーチカ・ナームローゼ・フエンノートシヤツプ | グリシン輸送阻害剤 |
CN1292698A (zh) * | 1998-03-06 | 2001-04-25 | 詹森药业有限公司 | 甘氨酸传递抑制剂 |
GB0021419D0 (en) | 2000-08-31 | 2000-10-18 | Oxford Glycosciences Uk Ltd | Compounds |
AR032653A1 (es) * | 2001-02-09 | 2003-11-19 | Telik Inc | Inhibidores heterociclicos del trasportador de glicina 2 composiciones farmaceuticas, uso y metodos. |
AU2002344951A1 (en) | 2001-07-02 | 2003-01-21 | Boehringer Ingelheim International Gmbh | Substituted piperazine and diazepanes as histamine h3 receptor agonists |
WO2003035602A1 (fr) | 2001-10-25 | 2003-05-01 | Sankyo Company, Limited | Modulateurs lipidiques |
DE10217006A1 (de) * | 2002-04-16 | 2003-11-06 | Merck Patent Gmbh | Substituierte Indole |
WO2004037800A1 (en) * | 2002-10-22 | 2004-05-06 | Glaxo Group Limited | Aryloxyalkylamine derivates as h3 receptor ligands |
ATE382611T1 (de) * | 2003-08-11 | 2008-01-15 | Hoffmann La Roche | Piperazin mit or-substituierter phenylgruppe und deren verwendung als glyt1-inhibitoren |
RU2355683C2 (ru) | 2003-09-09 | 2009-05-20 | Ф.Хоффманн-Ля Рош Аг | Производные 1-бензоилпиперазина в качестве ингибиторов поглощения глицина для лечения психозов |
CN1874777B (zh) | 2003-09-09 | 2012-07-04 | 弗·哈夫曼-拉罗切有限公司 | 作为甘氨酸摄取抑制剂用于治疗精神病的1-(2-氨基-苯甲酰基)-哌嗪衍生物 |
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2005
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- 2005-12-28 KR KR1020077018037A patent/KR100895752B1/ko not_active IP Right Cessation
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- 2005-12-28 JP JP2007549824A patent/JP5006799B2/ja not_active Expired - Fee Related
- 2005-12-28 AT AT05824313T patent/ATE472327T1/de active
- 2005-12-28 RU RU2007124545/04A patent/RU2396270C2/ru not_active IP Right Cessation
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Also Published As
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EP1838308B1 (en) | 2010-06-30 |
EP1838308A1 (en) | 2007-10-03 |
CA2593463A1 (en) | 2006-07-13 |
CN101137363A (zh) | 2008-03-05 |
WO2006072436A1 (en) | 2006-07-13 |
NO20073667L (no) | 2007-07-24 |
RU2007124545A (ru) | 2009-02-20 |
TWI313174B (en) | 2009-08-11 |
CA2593463C (en) | 2013-10-08 |
IL184353A (en) | 2012-06-28 |
AU2005324024A1 (en) | 2006-07-13 |
IL184353A0 (en) | 2007-10-31 |
AR052866A1 (es) | 2007-04-11 |
DE602005022113D1 (de) | 2010-08-12 |
CN101137363B (zh) | 2010-09-15 |
US20060167009A1 (en) | 2006-07-27 |
ZA200705472B (en) | 2008-09-25 |
BRPI0519794A2 (pt) | 2009-03-17 |
ATE472327T1 (de) | 2010-07-15 |
MX2007008189A (es) | 2007-08-07 |
TW200635585A (en) | 2006-10-16 |
KR20070092759A (ko) | 2007-09-13 |
KR100895752B1 (ko) | 2009-04-30 |
US7220744B2 (en) | 2007-05-22 |
RU2396270C2 (ru) | 2010-08-10 |
JP2008526796A (ja) | 2008-07-24 |
AU2005324024B2 (en) | 2011-02-17 |
ES2346335T3 (es) | 2010-10-14 |
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